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    Comparison of brucellar and tuberculous spondylodiscitis patients: results of the multicenter Backbone-1 Study
    (Elsevier Science Inc, 2015) Erdem, Hakan; Elaldi, Nazif; Batirel, Ayse; Aliyu, Sani; Sengoz, Gonul; Pehlivanoglu, Filiz; Ramosaco, Ergys
    BACKGROUND CONTEXT: No direct comparison between brucellar spondylodiscitis (BSD) and tuberculous spondylodiscitis (TSD) exists in the literature. PURPOSE: This study aimed to compare directly the clinical features, laboratory and radiological aspects, treatment, and outcome data of patients diagnosed as BSD and TSD. STUDY DESIGN: A retrospective, multinational, and multicenter study was used. PATIENT SAMPLE: A total of 641 (TSD, 314 and BSD, 327) spondylodiscitis patients from 35 different centers in four countries (Turkey, Egypt, Albania, and Greece) were included. OUTCOME MEASURES: The pre- and peri- or post-treatment spinal deformity and neurologic deficit parameters, and mortality were carried out. METHODS: Brucellar spondylodiscitis and TSD groups were compared for demographics, clinical, laboratory, radiological, surgical interventions, treatment, and outcome data. The Student t test and Mann-Whitney U test were used for group comparisons. Significance was analyzed as two sided and inferred at 0.05 levels. RESULTS: The median baseline laboratory parameters including white blood cell count, C-reactive protein, and erythrocyte sedimentation rate were higher in TSD than BSD (p<.0001). Prevertebral, paravertebral, epidural, and psoas abscess formations along with loss of vertebral corpus height and calcification were significantly more frequent in TSD compared with BSD (p<.01). Surgical interventions and percutaneous sampling or abscess drainage were applied more frequently in TSD (p<.0001). Spinal complications including gibbus deformity, kyphosis, and scoliosis, and the number of spinal neurologic deficits, including loss of sensation, motor weakness, and paralysis were significantly higher in the TSD group (p<.05). Mortality rate was 2.22% (7 patients) in TSD, and it was 0.61% (2 patients) in the BSD group (p=.1). CONCLUSIONS: The results of this study show that TSD is a more suppurative disease with abscess formation requiring surgical intervention and characterized with spinal complications. We propose that using a constellation of constitutional symptoms (fever, back pain, and weight loss), pulmonary involvement, high inflammatory markers, and radiological findings will help to differentiate between TSD and BSD at an early stage before microbiological results are available. (C) 2015 Elsevier Inc. All rights reserved.
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    Cranial imaging findings in neurobrucellosis: results of Istanbul-3 study
    (Springer Heidelberg, 2016) Erdem, Hakan; Senbayrak, Seniha; Meric, Kaan; Batirel, Ayse; Karahocagil, Mustafa Kasim; Hasbun, Rodrigo; Sengoz, Gonul
    Objective Neuroimaging abnormalities in central nervous system (CNS) brucellosis are not well documented. The purpose of this study was to evaluate the prevalence of imaging abnormalities in neurobrucellosis and to identify factors associated with leptomeningeal and basal enhancement, which frequently results in unfavorable outcomes. Methods Istanbul-3 study evaluated 263 adult patients with CNS brucellosis from 26 referral centers and reviewed their 242 magnetic resonance imaging (MRI) and 226 computerized tomography (CT) scans of the brain. Results A normal CT or MRI scan was seen in 143 of 263 patients (54.3 %). Abnormal imaging findings were grouped into the following four categories: (a) inflammatory findings: leptomeningeal involvements (44), basal meningeal enhancements (30), cranial nerve involvements (14), spinal nerve roots enhancement (8), brain abscesses (7), granulomas (6), and arachnoiditis (4). (b) White-matter involvement: white-matter involvement (32) with or without demyelinating lesions (7). (c) Vascular involvement: vascular involvement (42) mostly with chronic cerebral ischemic changes (37). (d) Hydrocephalus/cerebral edema: hydrocephalus (20) and brain edema (40). On multivariate logistic regression analysis duration of symptoms since the onset (OR 1.007; 95 % CI 1-28, p = 0.01), polyneuropathy and radiculopathy (OR 5.4; 95 % CI 1.002-1.013, p = 0.044), cerebrospinal fluid (CSF)/serum glucose rate (OR 0.001; 95 % CI 000-0.067, p = 0.001), and CSF protein (OR 2.5; 95 % CI 2.32.7, p = 0.0001) were associated with diffuse inflammation. Conclusions In this study, 45 % of neurobrucellosis patients had abnormal neuroimaging findings. The duration of symptoms, polyneuropathy and radiculopathy, high CSF protein level, and low CSF/serum glucose rate were associated with inflammatory findings on imaging analyses.
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    Hamsi scoring in the prediction of unfavorable outcomes from tuberculous meningitis: results of Haydarpasa-II study
    (Springer Heidelberg, 2015) Erdem, Hakan; Ozturk-Engin, Derya; Tireli, Hulya; Kilicoglu, Gamze; Defres, Sylviane; Gulsun, Serda; Sengoz, Gonul
    Predicting unfavorable outcome is of paramount importance in clinical decision making. Accordingly, we designed this multinational study, which provided the largest case series of tuberculous meningitis (TBM). 43 centers from 14 countries (Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria, Turkey) submitted data of microbiologically confirmed TBM patients hospitalized between 2000 and 2012. Unfavorable outcome was defined as survival with significant sequela or death. In developing our index, binary logistic regression models were constructed via 200 replicates of database by bootstrap resampling methodology. The final model was built according to the selection frequencies of variables. The severity scale included variables with arbitrary scores proportional to predictive powers of terms in the final model. The final model was internally validated by bootstrap resampling. A total of 507 patients' data were submitted among which 165 had unfavorable outcome. Eighty-six patients died while 119 had different neurological sequelae in 79 (16 %) patients. The full model included 13 variables. Age, nausea, vomiting, altered consciousness, hydrocephalus, vasculitis, immunosuppression, diabetes mellitus and neurological deficit remained in the final model. Scores 1-3 were assigned to the variables in the severity scale, which included scores of 1-6. The distribution of mortality for the scores 1-6 was 3.4, 8.2, 20.6, 31, 30 and 40.1 %, respectively. Altered consciousness, diabetes mellitus, immunosuppression, neurological deficits, hydrocephalus, and vasculitis predicted the unfavorable outcome in the scoring and the cumulative score provided a linear estimation of prognosis.
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    Hydrocephalus and vasculitis delay therapeutic responses in tuberculous meninigitis: Results of Haydarpasa-III study
    (Medknow Publications & Media Pvt Ltd, 2016) Cag, Yasemin; Ozturk-Engin, Derya; Gencer, Serap; Hasbun, Rodrigo; Sengoz, Gonul; Crisan, Alexandru; Ceran, Nurgul
    Aims: There is no report on the factors affecting the resolution of symptoms related to meningitis during treatment of tuberculous meningitis (TBM). Thus, we examined the factors associated with early therapeutic responses. Materials and Methods: This multicenter study included 507 patients with microbiologically confirmed TBM. However, 94 patients eligible for the analysis were included in this study from 24 centers. Six out of 94 patients died and the statistical analysis was performed with 88 survivors. Early and late responder groups were compared in the statistical analysis. P < 0.05 were considered to show a significant difference. Results: In the multivariate analysis, the presence of vasculitis (P = 0.029, OR = 10.491 [95% CI, 1.27u86.83]) was found to be significantly associated with a delayed fever response whereas hydrocephalus was associated with altered mental status for 9 days duration (P = 0.005, OR = 5.740 [95% CI, 1.68u19.57]). According to linear regression analysis, fever was significantly persisting (7 days) in the presence of vasculitis (17.5 vs. 7, P< 0.001) and hydrocephalus (11 vs. 7, P = 0.029). Hydrocephalus was significantly associated with persisting headache (21 vs. 12, P = 0.025), delayed recovery of consciousness (19.5 vs. 7, P = 0.001), and a delay in complete recovery (21 vs. 14, P = 0.007) in the linear regression analysis. Following institution of treatment, the complaints seemed to disappear in up to 2 weeks among TBM survivors. Conclusions: In the absence of hydrocephalus or vasculitis, one week of anti-tuberculosis treatment seems to be adequate for the resolution of TBM symptoms. Hydrocephalus and vasculitis delay the resolution of TBM symptoms in response to antimycobacterial treatment.
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    Mortality indicators in pneumococcal meningitis: therapeutic implications
    (Elsevier Sci Ltd, 2014) Erdem, Hakan; Elaldi, Nazif; Oztoprak, Nefise; Sengoz, Gonul; Ak, Oznur; Kaya, Selcuk; Inan, Asuman
    Background: The aim of this study was to delineate mortality indicators in pneumococcal meningitis with special emphasis on therapeutic implications. Methods: This retrospective, multicenter cohort study involved a 15-year period (1998-2012). Culture-positive cases (n = 306) were included solely from 38 centers. Results: Fifty-eight patients received ceftriaxone plus vancomycin empirically. The rest were given a third-generation cephalosporin alone. Overall, 246 (79.1%) isolates were found to be penicillin-susceptible, 38 (12.2%) strains were penicillin-resistant, and 22 (7.1%) were oxacillin-resistant (without further minimum inhibitory concentration testing for penicillin). Being a critical case (odds ratio (OR) 7.089, 95% confidence interval (CI) 3.230-15.557) and age over 50 years (OR 3.908, 95% CI 1.820-8.390) were independent predictors of mortality, while infection with a penicillin-susceptible isolate (OR 0.441, 95% CI 0.195-0.996) was found to be protective. Empirical vancomycin use did not provide significant benefit (OR 2.159, 95% CI 0.949-4.912). Conclusions: Ceftriaxone alone is not adequate in the management of pneumococcal meningitis due to penicillin-resistant pneumococci, which is a major concern worldwide. Although vancomycin showed a trend towards improving the prognosis of pneumococcal meningitis, significant correlation in statistical terms could not be established in this study. Thus, further studies are needed for the optimization of pneumococcal meningitis treatment. (C) 2013 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. All rights reserved.
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    Tuberculous and brucellosis meningitis differential diagnosis
    (Elsevier Sci Ltd, 2015) Erdem, Hakan; Senbayrak, Seniha; Gencer, Serap; Hasbun, Rodrigo; Karahocagil, Mustafa Kasim; Sengoz, Gonul; Karsen, Hasan
    Background: The Thwaites and Lancet scoring systems have been used in the rapid diagnosis of tuberculous meningitis (TBM). However, brucellar meningoencephalitis (BME) has similar characteristics with TBM. The ultimate aim of this study is to infer data to see if BME should be included in the differential diagnosis of TBM when these two systems suggest the presence of TBM. Method: BME and TBM patients from 35 tertiary hospitals were included in this study. Overall 294 adult patients with BME and 190 patients with TBM were enrolled. All patients involved in the study had microbiological confirmation for either TBM or BME. Finally, the Thwaites and Lancet scoring systems were assessed in both groups. Results: The Thwaites scoring system more frequently predicted BME cases (n = 292, 99.3%) compared to the TBM group (n = 182, 95.8%) (P = 0.017). According to the Lancet scoring system, the mean scores for BME and TBM were 9.43 +/- 1.71 and 11.45 +/- 3.01, respectively (P < 0.001). In addition, TBM cases were classified into probable category more significantly compared to BME cases, and BME cases were categorized into the possible category more frequently. Conclusions: When the Thwaites or Lancet scoring systems indicate TBM, brucellar etiology should also be taken into consideration particularly in endemic countries. (C) 2015 Elsevier Ltd. All rights reserved.